Possible interethnic differences in quinidine-induced QT prolongation between healthy Caucasian and Korean subjects

초록

Aims The aim of this study was to evaluate the pharmacokinetics and pharmacodynamics of quinidine-induced QT prolongation in healthy Caucasian and Korean subjects to investigate interethnic differences in susceptibility to drug-induced arrhythmia. Methods A randomized, double-blind crossover study was conducted in 24 ( 12 male and 12 female) Korean and 13 ( seven male and six female) Caucasian subjects. After a 20 min infusion of quinidine ( 4 mg kg(-1)) or saline, the serum concentration of quinidine and the QT interval corrected by Bazett's formula (QTc) were monitored. The dynamic data were analyzed by means of a population modelling approach using NONMEM. Results There were no statistical differences in the pharmacokinetic profiles of quinidine between ethnic groups. The QTc values in Caucasians were higher than those in Koreans at the same quinidine concentrations, especially at higher quinidine concentrations and in female subjects. According to an E-max model (E-t = E-0 + Delta E-max[C-t]/EC50 + [C-t]), the population modelling approach revealed that E-0 (ms) was related to gender (408 + [34*(1-Sex)]; 1 for male and 0 for female), Delta E-max (ms) was related to ethnicity ((136*f(ETHN)) + C-female: f(ETHN) = 1 for Koreans and 1.26 for Caucasians; C-female was 106 only for Caucasian females), and EC50 was estimated to be 3.13 mu m. Conclusions These results suggest that Korean subjects were less sensitive to quinidine-induced QT prolongation than Caucasian subjects, and that this trend was particularly true for females. Further population-based studies are merited to characterize more completely the ethnic differences in drug-induced QT prolongation between Asians and other ethnic groups.

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